The research focus of the Unit of Molecular Virology in the Laboratory of Cell Biology has been the determination of the individual steps in the complex process of retroviral infection. The first stage of infection requires virus binding to a cell surface receptor. We had previously determined that the human receptor for Gibbon Ape Leukemia Virus (GALV) is a phosphate symporter. We have now identified specific residues within a small extracellular region of the GALV receptor that are involved in viral entry. An improved understanding of the requirements for optimal receptor-retrovirus interactions is critical in order to modify retroviral vectors to target cells more specifically. We have initiated studies to map the region(s) of the GALV envelope that specifically interacts with the human form of the GALV receptor. After binding of the envelope protein to its receptor, the virus envelope and the cell membrane fuse and the virion core is released into the cytoplasm. We have determined that the ability of a virus to fuse and enter a target cell is independent of its ability to bind its receptor. Different regions within the viral envelope are involved in binding and fusion. After entry of the core into the cytoplasm, the process of reverse transcription of the RNA genome into DNA and transport to the nucleus of the cells is dependent on core protein functions. Genome and core components are required for integration into the host cell chromosome. Retroviral infection is dependent on the efficient function of each of these three components (envelope, core and genome) of the retrovirus governing specific stages in the infection. We are constructing retroviral vectors in which these components are optimized for specific human target cells.